Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells
Chitra Thakur,
Yiran Qiu,
Qian Zhang,
Nicholas J. Carruthers,
Miaomiao Yu,
Zhuoyue Bi,
Yao Fu,
Priya Wadgaonkar,
Bandar Almutairy,
Akimasa Seno,
Paul M. Stemmer,
Fei Chen
Affiliations
Chitra Thakur
Stony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USA
Yiran Qiu
Stony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USA
Qian Zhang
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA
Nicholas J. Carruthers
Institute of Environmental Health Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA
Miaomiao Yu
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; Cancer Hospital of China Medical University, 44 Xiaoheyan Road, Dadong District, Shenyang, 110042 Liaoning Province, China
Zhuoyue Bi
Stony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USA
Yao Fu
Stony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USA
Priya Wadgaonkar
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA
Bandar Almutairy
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; College of Pharmacy, Al-Dawadmi Campus, Shaqra University, P.O. Box 11961, Riyadh, Saudi Arabia
Akimasa Seno
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; Faculty of Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, Japan
Paul M. Stemmer
Institute of Environmental Health Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA
Fei Chen
Stony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USA; Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; Corresponding author
Summary: In this report, we provide evidence showing diminished expression of the mineral dust-induced gene (mdig), a previously identified oncogenic gene, in human triple negative breast cancer (TNBC). Using a mouse model of orthotopic xenograft of the TNBC MDA-MB-231 cells, we demonstrate that mdig promotes the growth of primary tumors but inhibits metastasis of these cells in vivo. Knockout of mdig resulted in an enhancement of H3K36me3 in the genome and upregulation of some X chromosome-linked genes for cell motility, invasion, and metastasis. Silencing MAGED2, one of the most upregulated and H3K36me3-enriched genes resulted from mdig depletion, can partially reverse the invasive migration of the mdig knockout cells. The anti-metastatic and inhibitory role of mdig on H3K36me3 was cross-validated in another cell line, A549 lung cancer cells. Together, our data suggest that mdig is antagonist against H3K36me3 that enforces expression of genes, such as MAGED2, for cell invasion and metastasis.
